TWI781268B - Ophthalmic article and masking method - Google Patents

Abstract

The present invention is an ophthalmic product, which is obtained by storing an ophthalmic composition in a container, and enclosing and sealing the container together with an iron-based oxygen absorber with an encapsulating body. The body and the cover of the composition, the ophthalmic composition comprises: (A) easily oxidized, (B) cooling agents, (C) nonionic surfactants, and (D) selected from dibutyl One or more components of hydroxytoluene, dibutyl hydroxyanisole, propyl peroxybenzoate, butyl peroxybenzoate and chlorobutanol, in the ophthalmic product, the volume of the body is 1mL~ 25mL, the oxygen permeability of the body is 10cc/(m ² .24hr.atm) or more, and the volume of the space formed between the envelope and the container is 200V/ Below V%.

Description

Ophthalmic preparations and masking methods

The present invention relates to an ophthalmic product and a masking method in which the odor of an oxygen absorbing agent is suppressed.

As a method of stabilizing easily oxidizable components, a method using an oxygen absorbing agent is known. In the field of eye drops, it is also known that the oxygen in the container can be absorbed by enclosing the eye drops and oxygen absorbing agent contained in the container, thereby stabilizing easily oxidizable substances in the eye drops. Chemical (Japanese Patent Laid-Open Publication No. 6-40907). On the other hand, active ingredients such as fat-soluble vitamin A act as an anti-cornea. Active ingredients for the conjunctiva, nasal mucosa, or pharynx have attracted attention, but these active ingredients have a characteristic odor, and the odor increases over time.

[Prior art literature] [Patent Document]

[Patent Document 1] Japanese Patent Laid-Open No. 6-40907

However, it has been found that if an oxygen absorber mainly composed of iron (hereinafter also referred to as an iron-based oxygen absorber) is placed in the package for long-term storage, the following problems will occur: Burnt-like special odor, and attached to the capsule On or filled in the package body, so you will feel the smell when you open the package. On the other hand, active ingredients such as fat-soluble vitamin A act as an anti-cornea. Conjunctiva, nasal mucosa or pharynx are attracting attention as active ingredients. However, these active ingredients have a peculiar smell, and the smell increases with time. The use of an oxygen absorbing agent in ophthalmic preparations containing vitamin A is insufficient in terms of improvement of the odor at the time of opening. From the above points, an ophthalmic composition containing easily oxidized substances such as vitamin A is housed in a container, and further surrounded and sealed by an encapsulating body together with an oxygen absorbing agent mainly composed of iron. In the product, it is a masking method to suppress the special odor when the package is opened due to deoxidation.

The inventors of the present invention have conducted diligent research to achieve the above-mentioned object, and as a result, it has been found that an ophthalmic composition containing easily oxidized substances such as vitamin A is housed in a container including a main body and a cover, and further combined with iron as a main component In an ophthalmic product that is surrounded and sealed by an encapsulation body together with an oxygen absorbing agent, the capacity of the body, the oxygen transmission rate of the body, and the space formed between the encapsulation body and the container The volume is set in a specific range, and the cooling agent volatilizes from the container, and volatilizes from the ophthalmic composition to the container, and then from the container to the encapsulating body. Retention, so that the odor (from the oxygen absorber and from the easy oxidation) generated when opening the seal can be masked easily and at low cost.

Accordingly, the present invention provides the following ophthalmic articles and masking methods.

[1]. An ophthalmic product, which is obtained by storing an ophthalmic composition in a container, and enclosing and sealing the container together with an iron-based oxygen absorbing agent, the container including A body and a cover of an ophthalmic composition, the ophthalmic composition comprising: (A) easily oxidized, (B) cooling agents, (C) nonionic surfactants, and (D) selected from dibutyl hydroxytoluene, dibutyl hydroxyanisole, propyl peroxybenzoate, butyl peroxybenzoate and chlorobutanol, in the ophthalmic product, the capacity of the body is 1mL ~25mL, the oxygen permeability of the body is above 10cc/(m ² .24hr.atm), and the volume of the space formed between the envelope and the container is 200V relative to the volume of the container /V% or less.

[2]. The ophthalmic product according to [1], wherein the component (A) is vitamin A.

[3]. The ophthalmic product as described in [1] or [2], wherein component (B) is selected from l-menthol, dl-camphor, d-camphor, d-borneol, geraniol and eucalyptus oil more than one of them.

[4]. The ophthalmic product according to any one of [1] to [3], wherein the compounding amount of the component (B) in the ophthalmic composition is 0.0001 w/v% or more.

[5]. The ophthalmic product as described in any one of [1] to [4], wherein component (C) is selected from polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene (20) At least one of sorbitan oleate and polyoxyethylene polyoxypropylene glycol.

[6]. A masking method for masking an odor when an encapsulated body is unsealed in an ophthalmic product, wherein an ophthalmic composition is housed in a container, and the container and the container are separated by the encapsulated body. The iron-based oxygen absorber is surrounded and sealed together. The container includes a body and a cover for containing the ophthalmic composition. The ophthalmic composition includes: (A) easily oxidized, (B) cooling agent , (C) nonionic surfactant, and (D) selected from dibutyl hydroxytoluene, dibutyl hydroxyanisole, propyl peroxybenzoate, butyl peroxybenzoate and chlorobutanol One or more ingredients, the masking method is in the ophthalmic product, the volume of the body is set to 1mL~25mL, and the oxygen transmission rate of the body is set to 10cc/(m ² .24hr.atm) or more The volume of the space formed between the envelope and the container is 200 V/V% or less relative to the volume of the container.

According to the present invention, it is possible to provide an ophthalmic product in which an ophthalmic composition containing easily oxidized substances and an oxygen absorbing agent mainly composed of iron are packaged in an encapsulation body, and the special performance when the encapsulation body is opened can be provided. An ophthalmic article with suppressed odor, and a masking method.

Hereinafter, the present invention will be described in detail.

[Ophthalmic Composition]

The ophthalmic composition of the present invention comprises (A) an easily oxidized product, (B) a cooling agent, (C) a nonionic surfactant, and (D) a One or more of ether, propyl peroxybenzoate, butyl peroxybenzoate, and chlorobutanol.

[(A) ingredient]

As (A) easy oxides, any of water-soluble easy oxides and hydrophobic easy oxides can be used, and it can be used individually by 1 type or in combination of 2 or more types suitably. Examples of water-soluble easily oxidized substances include: sodium azulene sulfonate, vitamin B ₂ (flavin adenine dinucleotide (flavin adenine dinucleotide), etc.), vitamin B ₆ (pyridoxine hydrochloride (pyridoxine hydrochloride) etc.), vitamin B ₁₂ (cyanocobalamin etc.), vitamin C (ascorbic acid etc.) etc.

As hydrophobic easily oxidized substances, ingredients included in the Japanese Pharmacopoeia, Japanese Pharmacopoeia Standards for External Drugs, Encyclopedia of Pharmaceutical Additives, Standards for Pharmaceutical Additives, Standards for Cosmetic Raw Materials, Standards for Cosmetic Compounding Ingredients, and Food Additives can be used The solubility in water in medium ranges from "slightly insoluble" to "almost insoluble" substances, and includes all substances that can undergo oxidative decomposition. Specific examples of easily oxidized substances include vitamin A, vitamin D, vitamin E, vitamin K, diphenhydramine, indomethacin, tacrolimus (FK506), Macrolide antibiotics such as rifampicin, forskolin, etc., but are not limited to these substances.

Among them, vitamin A can promote corneal and conjunctival repair, promote mucin production, improve dry eye, and eye fatigue. Eye blur improvement effect, and easy to break down Go out unique bad smell, therefore can further bring into play the effect of the present invention. Examples of the vitamin A include vitamin A itself, vitamin A-containing mixtures such as vitamin A oil, vitamin A derivatives such as vitamin A fatty acid esters, and the like. Specifically, retinyl palmitate, retinyl acetate, retinol, retinoic acid, retinoids, β-carotene, etc. are mentioned. Among them, retinyl palmitate and retinyl acetate are preferable, and retinyl palmitate is more preferable.

Retinyl palmitate is usually commercially available with 1 million international units/g to 1.8 million international units/g (hereinafter sometimes abbreviated as IU/g), specifically, DSM Nutrition Japan (DSM Nutrition Japan) ) Co., Ltd. retinyl palmitate (1.74 million I.U.), retinyl palmitate manufactured by Sigma-Aldrich, etc.

Examples of vitamin D include vitamin D3 (cholecalciferol), 1α,25-dihydroxyvitamin D3, and derivatives thereof. Examples of vitamin E include α-tocopherol, d-α-tocopheryl acetate, and derivatives thereof, and examples of vitamin K include vitamin K1 (phytylmenadione) and derivatives thereof. Among them, fat-soluble vitamins such as retinyl palmitate and d-α-tocopheryl acetate, tacrolimus (FK506), Rifampin, macrolide antibiotics, forskolin, etc.

The blending amount of the component (A) in the ophthalmic composition is preferably 0.005w/v%~2w/v% (mass/volume%, g/100mL, the same below), more preferably 0.01w/v%~1w /v%. Furthermore, in the case of formulating vitamin A, it is preferably 5,000IU/100mL~300,000IU/100mL, more preferably 5,000IU/100mL~100,000 IU/100mL, and more preferably 5,000IU/100mL~50,000IU/100mL. When the concentration of vitamin A is high, the effects on the eyes (promotion of corneal and conjunctival repair, promotion of mucin production, dry eye improvement effect, eye fatigue, and eye blur improvement effect) are further improved.

[(B) component]

Examples of cooling agents include l-menthol, dl-camphor, d-camphor, d-borneol, eucalyptus oil, bergamot oil, geraniol, linalool, eucalyptol, anise oil, Peppermint oil, peppermint oil, rose oil, wild peppermint oil, peppermint oil, and the like can be used alone or in combination of two or more as appropriate. Among them, l-menthol, dl-camphor, d-camphor, d-borneol, geraniol, and eucalyptus oil are preferable.

In terms of masking, the blending amount of component (B) in the ophthalmic composition is preferably at least 0.0001w/v%, more preferably 0.0001w/v%~0.5w/v%, and still more preferably 0.00015 w/v%~0.2w/v%, preferably 0.0002w/v%~0.1w/v%. If the compounding amount is too large, the irritation at the time of instillation will be strong, and the usability may be impaired.

As the cooling agent of the present invention, in the case of formulating (B-1) l-menthol, it is preferably 0.005w/v%~0.5w/v%, more preferably 0.01w/v%~0.2w/ v%, more preferably 0.02w/v%~0.1w/v%, more preferably 0.03w/v%~0.1w/v%, most preferably 0.04w/v%~0.05w/v%. If the compounding amount is too large, the eye-dropping irritation may be strong, and the feeling of use may be impaired, and if it is too small, the masking effect may be insufficient.

As the cooling agent of the present invention, in the case of deploying (B-2) camphor, it is preferably 0.002w/v%~0.5w/v%, more preferably 0.005w/v%~0.2w/v%, Further preferably, it is 0.01w/v% to 0.1w/v%. If the deployment amount is too much, it will cause irritation when dropping the eyes. If it is strong, the usability may be impaired, and if it is too small, the masking effect will be insufficient.

As the cooling agent of the present invention, in the case of blending (B-3)d-borneol and geraniol, it is preferably 0.002w/v%~0.5w/v%, more preferably 0.003w/v%~ 0.2w/v%, more preferably 0.005w/v%~0.1w/v%. If the compounding amount is too large, the eye-dropping irritation may be strong, and the feeling of use may be impaired, and if it is too small, the masking effect may be insufficient.

As the cooling agent of the present invention, in the case of formulating (B-4) eucalyptus oil, it is preferably 0.0005w/v%~0.5w/v%, more preferably 0.001w/v%~0.2w/v% , and more preferably 0.0015w/v%~0.1w/v%. If the compounding amount is too large, the eye-dropping irritation may be strong, and the feeling of use may be impaired, and if it is too small, the masking effect may be insufficient.

[(C) ingredient]

As a nonionic surfactant, it will not specifically limit if it can be used for an ophthalmic composition, One type can be used individually or in combination of 2 or more types suitably. For example, polyoxyethylene sorbitan fatty acid represented by polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene (20) sorbitan oleate (polysorbate 80) Ester (POE (polyoxyethylene) sorbitan fatty acid ester), polyoxyethylene polyoxypropylene glycol represented by poloxamer (polyoxyethylene polyoxypropylene block copolymer, POEPOP (polyoxyethylene polyoxypropylene) glycol), polyethylene glycol monostearate represented by polyethylene glycol monostearate (10), and the like.

Polyoxyethylene castor oil (POE castor oil) is a compound obtained by adding polymerized ethylene oxide (EO) to castor oil, and is known to have oxygen Several species with different average addition moles of ethylene. The average number of moles of ethylene oxide added to polyoxyethylene castor oil is not particularly limited, and can be, for example, 3 moles to 60 moles. Specifically, polyoxyethylene castor oil 3 (the average molar number of EO added is 3), polyoxyethylene castor oil 10 (the average molar number of EO added is 10), polyoxyethylene castor oil 20 ( The average added molar number of EO is 20), polyoxyethylene castor oil 35 (the average added molar number of EO is 35), polyoxyethylene castor oil 40 (the average added molar number of EO is 40), polyoxyethylene castor oil Castor oil 50 (the average number of added moles of EO is 50), polyoxyethylene castor oil 60 (the average number of added moles of EO is 60), etc.

Polyoxyethylene hydrogenated castor oil (POE hydrogenated castor oil) is a compound obtained by adding and polymerizing ethylene oxide to hydrogenated castor oil, and several types are known in which the average molar number of added ethylene oxide is different. The average added mole number of ethylene oxide in polyoxyethylene hydrogenated castor oil is not particularly limited, and may be 5 to 100 moles as an example. Specifically, polyoxyethylene hydrogenated castor oil 5 (the average molar number of EO added is 5), polyoxyethylene hydrogenated castor oil 10 (the average molar number of EO added is 10), polyoxyethylene hydrogenated castor oil Sesame oil 20 (the average added molar number of EO is 20), polyoxyethylene hydrogenated castor oil 30 (the average added molar number of EO is 30), polyoxyethylene hydrogenated castor oil 40 (the average added molar number of EO is 40 ), polyoxyethylene hydrogenated castor oil 50 (the average molar number of EO added is 50), polyoxyethylene hydrogenated castor oil 60 (the average molar number of EO added is 60), polyoxyethylene hydrogenated castor oil 80 (the average molar number of EO added Addition mole number is 80), polyoxyethylene hydrogenated castor oil 100 (the average addition mole number of EO is 100), etc.

Examples of polyoxyethylene sorbitan fatty acid esters (POE sorbitan fatty acid esters) include polyoxyethylene monolaurate (20) sorbitan (polysorbate Sugar alcohol ester 20), polyoxyethylene monopalmitate (20) sorbitan (polysorbate 40), polyoxyethylene monostearate (20) sorbitan (polysorbate 60) , Polyoxyethylene tristearate (20) sorbitan (polysorbate 65), polyoxyethylene monooleate (20) sorbitan (polysorbate 80).

Polyoxyethylene polyoxypropylene diol (POEPOP diol) is a block copolymer comprising polyoxyethylene chain (POE) and polyoxypropylene chain (POP), and known as ethylene oxide (EO) and propylene oxide (PO ) with different average added moles. The average addition mole number of ethylene oxide and propylene oxide in polyoxyethylene polyoxypropylene glycol is not particularly limited, and the average addition mole number is 5 moles to 200 moles. Specifically, polyoxyethylene (200) polyoxypropylene (70) diol (the average added molar number of EO is 200, and the average added molar number of PO is 70), polyoxyethylene (196) polyoxypropylene ( 67) Diol (the average molar addition of EO is 196, the average molar addition of PO is 67), polyoxyethylene (160) polyoxypropylene (30) diol (the average molar addition of EO is 160, and the average molar addition of PO is 67) Added molar number 30), polyoxyethylene (120) polyoxypropylene (40) diol (EO average added molar number 120, PO average added molar number 40), polyoxyethylene (42) polyoxyethylene Propylene (67) diol (the average molar addition of EO is 42, the average molar addition of PO is 67), polyoxyethylene (54) polyoxypropylene (39) diol (the average molar addition of EO is 54, The average added molar number of PO is 39), polyoxyethylene (20) polyoxypropylene (20) diol (the average added molar number of EO is 20, and the average added molar number of PO is 20), etc.

Among them, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene (20) sorbitan oleate and polyoxyethylene polyoxypropylene diol.

Regarding the compounding amount of (C) component in the ophthalmic composition, in the case of compounding polyoxyethylene polyoxypropylene glycol, it is preferably 0.001w/v%~5.0w/v%, more preferably 0.001w/v% v%~2.0w/v%, more preferably 0.001w/v%~1.0w/v%. When compounding (C) component other than polyoxyethylene polyoxypropylene glycol, it is preferably 0.001w/v%~0.5w/v%, more preferably 0.001w/v%~0.3w/v%, Further preferably, it is 0.001w/v%~0.2w/v%. If the compounding amount of the component (C) is too large, the cooling agent may be contained in the active agent colloids and volatilization may be suppressed, and if it is too small, the cooling agent or the fat-soluble easily oxidized substance may be separated.

[(D) ingredient]

(D) The component is selected from butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), propyl peroxybenzoate, butyl peroxybenzoate and chlorobutanol one or more of the ingredients. Among them, dibutylhydroxytoluene is preferred. As (D)component, it can use individually by 1 type or in combination of 2 or more types suitably. The solubility of component (D) is lower than that of component (B), and it is easy to be included in the active agent colloid, so the volatilization of (B) cooling agent is further promoted, and the odor masking effect of (B) cooling agent is improved. .

The compounding amount of (D) component in an ophthalmic composition is preferably 0.001w/v% in terms of masking effect when dibutylhydroxytoluene and dibutylhydroxyanisole are compounded above, more preferably at least 0.002w/v%, further preferably at least 0.003w/v%. The upper limit is not particularly limited, and may be 0.01 w/v% or less.

In the case of formulating propyl peroxybenzoate and butyl peroxybenzoate, in terms of masking effect, it is preferably 0.03w/v% or more, more preferably 0.05w/v% or more, and even more preferably 0.1w/v% or more. The upper limit is not particularly limited, and may be 1 w/v% or less.

When compounding chlorobutanol, it is preferably at least 0.03 w/v%, more preferably at least 0.05w/v%, and still more preferably at least 0.1w/v%, from the viewpoint of the masking effect. The upper limit is not particularly limited, and may be 3 w/v% or less.

The preferable range of the compounding ratio (mass ratio) represented by (B)/(D) is as follows. In addition, although this ratio is a w/v% ratio, it is the same as a mass ratio (the same applies hereinafter). When the component (D) is (D-I) dibutyl hydroxytoluene or dibutyl hydroxyanisole, and when the component (D) is (D-II) propyl peroxybenzoate or butyl peroxybenzoate , The case where the component (D) is (D-III) chlorobutanol will be described.

(I) When the component (D) is dibutyl hydroxytoluene (BHT) or dibutyl hydroxy anisole (BHA), it is preferably 0.05~500, more preferably 0.1~200, and more preferably 0.1~100.

When l-menthol is compounded as (B) component, it is preferably 1.0-200, more preferably 2.0-100, still more preferably 3.0-50, especially preferably 4.0-50.

When compounding camphor (dl-camphor, d-camphor) as (B) component, it is preferable that it is 0.4-200, it is more preferable that it is 1.0-100, and it is more preferable that it is 2.0-50.

When compounding d-borneol or geraniol as (B) component, it is preferable that it is 0.4-200, it is more preferable that it is 0.6-100, and it is still more preferable that it is 1.0-50.

In the case of blending eucalyptus oil as component (B), it is preferably 0.1~ 200, more preferably 0.2-100, further preferably 0.3-50.

(II) When (D) component is propyl peroxybenzoate or butyl peroxybenzoate, it is preferable that it is 0.001-200, it is more preferable that it is 0.003-100, and it is more preferable that it is 0.01-50.

When compounding l-menthol as (B) component, it is preferable that it is 0.1-100, it is more preferable that it is 0.2-50, and it is still more preferable that it is 0.4-10.

When compounding camphor (dl-camphor, d-camphor) as (B) component, it is preferable that it is 0.05-100, it is more preferable that it is 0.15-50, and it is still more preferable that it is 0.2-10.

When compounding d-borneol or geraniol as (B) component, it is preferable that it is 0.05-100, it is more preferable that it is 0.1-50, and it is still more preferable that it is 0.15-10.

When compounding eucalyptus oil as (B) component, it is preferable that it is 0.01-100, it is more preferable that it is 0.02-50, and it is still more preferable that it is 0.05-10.

(III) When (D) component is chlorobutanol, it is preferable that it is 0.0001-100, it is more preferable that it is 0.0003-50, and it is more preferable that it is 0.0005-20 or more.

When compounding l-menthol as (B) component, it is preferable that it is 0.01-50, it is more preferable that it is 0.02-20, and it is still more preferable that it is 0.04-10.

When compounding camphor (dl-camphor, d-camphor) as (B) component, it is preferable that it is 0.05-50, it is more preferable that it is 0.15-20, and it is still more preferable that it is 0.2-10.

When compounding d-borneol or geraniol as (B) component, it is preferable that it is 0.0005-50, it is more preferable that it is 0.001-20, and it is still more preferable that it is 0.0015-10.

When compounding eucalyptus oil as (B) component, it is preferable that it is 0.001-50, it is more preferable that it is 0.002-20, and it is still more preferable that it is 0.005-10.

A preferable range of the compounding ratio (mass ratio) represented by ((B)+(D))/(C) is as follows. Furthermore, the case where (A) component is vitamin A, (C) component is (C-I) polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, or polyoxyethylene sorbitan fatty acid ester, (C) -II) The case of polyoxyethylene polyoxypropylene glycol is described.

When (A) component is vitamin A, the compounding ratio (mass ratio) represented by ((B)+(D))/(C) becomes like this. Preferably it is 0.01-30, More preferably, it is 0.02-10. If ((B)+(D))/(C) is too small, there is a risk that the cooling agent will be contained in the colloidal particles and the volatilization may be suppressed. If it is too large, there may be a risk of separation of the cooling agent or fat-soluble easily oxidized .

(C) When the component is (C-I) polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, or polyoxyethylene sorbitan fatty acid ester

When l-menthol is compounded as component (B) and dibutyl hydroxytoluene or dibutyl hydroxyanisole is compounded as component (D), it is preferably 0.05 to 15, more preferably 0.1 to 10 , and more preferably 0.15~5.

When compounding camphor (d-camphor, dl-camphor) as component (B) and dibutyl hydroxytoluene or dibutyl hydroxy anisole as component (D), it is preferably 0.04 to 5, More preferably, it is 0.05-4, More preferably, it is 0.08-3.

When compounding d-borneol or geraniol as component (B), and compounding dibutyl hydroxytoluene or dibutyl hydroxy anisole as component (D), it is preferably 0.03 to 5, more preferably 0.04~4, more preferably 0.05~3, especially preferably 0.06~3.

When blending eucalyptus oil as component (B) and dibutyl hydroxytoluene or dibutyl hydroxyanisole as component (D), it is preferably 0.02 to 5, more preferably 0.03 to 3, and further Preferably it is 0.04~3, especially preferably it is 0.045~3.

(C-II) In the case of polyoxyethylene polyoxypropylene glycol

When l-menthol is compounded as component (B) and dibutyl hydroxytoluene or dibutyl hydroxyanisole is compounded as component (D), it is preferably 0.005 to 1.5, more preferably 0.015 to 1.0 , and more preferably 0.025~0.5.

When compounding camphor (d-camphor, dl-camphor) as component (B) and dibutyl hydroxytoluene or dibutyl hydroxy anisole as component (D), it is preferably 0.007 to 0.5, More preferably, it is 0.01-0.4, More preferably, it is 0.015-0.3.

When compounding d-borneol or geraniol as component (B) and dibutyl hydroxytoluene or dibutyl hydroxy anisole as component (D), it is preferably 0.007 to 0.5, more preferably 0.008 to 0.4, more preferably 0.01 to 0.3.

When blending eucalyptus oil as component (B) and dibutyl hydroxytoluene or dibutyl hydroxy anisole as component (D), it is preferably 0.005 to 0.5, more preferably 0.006 to 0.4, and further Preferably it is 0.007~0.3.

In the above-mentioned (B)/(D) ratio and the compounding ratio represented by ((B)+(D))/(C), when compounding multiple (B) components, the total amount of (B) components The amount is regarded as the concentration of each component. Masking effect Eucalyptus oil, geraniol, d-borneol, camphor (d-camphor, dl-camphor), l-menthol in order from high to low, therefore, the ratio is in accordance with the masking in the formulated ingredients Range of ingredients with high effect. When compounding multiple types (C)component and (D)component, the total amount of each component is regarded as the density|concentration of each component. The range of ingredients that are more than the amount formulated.

[optional ingredient]

In the ophthalmic composition of this invention, various components which can be used for an ophthalmic composition can be mix|blended as needed within the range which does not impair the effect of this invention. Preferable formulation components include drugs, buffers, stabilizers, viscous agents, tonicity agents, antioxidants, preservatives, pH regulators, polyols, and the like.

Examples of drugs include: decongestant ingredients, eye muscle conditioning ingredients, anti-inflammatory ingredients or astringent ingredients, antihistamine ingredients or antiallergic ingredients, amino acids, antibacterial ingredients or bactericidal ingredients, sugars, Polysaccharides or their derivatives, local anesthetic ingredients, steroid ingredients, glaucoma treatment ingredients, cataract treatment ingredients, mydriatic ingredients, etc. Specific examples are shown below.

Decongestant ingredients: eg α-adrenaline agents such as imidazoline derivatives (naphazoline, tetrahydrozoline, etc.), β-phenethylamine derivatives (phenylephrine, epinephrine (epinephrine), ephedrine, methylephedrine, etc.), and their pharmaceutically or physiologically acceptable salts (such as naphazoline hydrochloride, naphazoline nitrate, tetrahydrozole hydrochloride Inorganic acid salts such as phylloline, tetrahydrozoline nitrate, phenylephrine hydrochloride, epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride; organic acid salts such as epinephrine bitartrate wait.

Ingredients of eye muscle regulating drugs: For example, cholinesterase inhibitors having an active center similar to acetylcholine (such as neostigmine methyl sulfate, etc.), tropicamide, and atropine sulfate (atropine) etc.

Anti-inflammatory or astringent ingredients: eg Pranoprofen (pranoprofen), celecoxib, rofecoxib, indomethacin, diclofenac, diclofenac sodium, piroxicam, meloxicam, aspirin (aspirin), mefenamic acid, indomethacin farnesil, acemetacin, ibuprofen, tiaprofenic acid, profenic acid Loxoprofen sodium, tiaramide hydrochloride, zinc salts (such as zinc sulfate, zinc lactate, etc.), lysozyme, lysozyme chloride, methyl salicylate, allantois ε-aminocaproic acid, berberine chloride, berberine sulfate, glycyrrhizic acid and pharmacologically acceptable salts (such as dipotassium glycyrrhizinate, ammonium glycyrrhizinate, etc.) and the like.

Antihistamine components or antiallergic components: Examples include ketotifen, acitazanolast, chlorpheniramine, diphenhydramine, levocabastine ( levocabastine), cromoglicic acid, tranilast, ibudilast, amlexanox, pemirolast, and their pharmaceutical or physiological Salts allowed above (diphenhydramine hydrochloride, ketotifen fumarate, sodium cromoglycate, etc.), etc.

Amino acid: for example, leucine (leucine), isoleucine, valine (valine), methionine (methionine), threonine (threonine), alanine (alanine), phenylalanine ( phenylalanine), tryptophan, lysine, glycine, serine, proline, tyrosine, cystine ), histidine (histidine), ornithine, hydroxyproline, hydroxylysine, glycylglycine, gamma-aminobutyric acid, glutamic acid, asparagine sodium aspartate, potassium aspartate, magnesium aspartate, aminoethylsulfonic acid (taurine) or a salt thereof (for example, cystine hydrochloride, etc.), and the like.

Antibacterial drug ingredients or bactericidal drug ingredients: for example, sulfonamides (such as sulfamethoxazole (sulfamethoxazole), sulfisoxazole (sulfisoxazole), sulfisomidine (sulfisomidine) and pharmacologically acceptable salts ( Sulfamethoxazole sodium, sulfamethazine sodium, etc.), rivanol (acrinol), alkyl polyaminoethyl glycine, new quinolone (new quinolone) agents (lomefloxacin, Levofloxacin (levofloxacin), ciprofloxacin (ciprofloxacin), ofloxacin (ofloxacin), norfloxacin (norfloxacin), ciprofloxacin hydrochloride, etc.), β-lactone antibiotics (sulbenicillin ( sulbenicillin), cefmenoxime (cefmenoxime, etc.), aminoglycoside antibiotics (kanamycin, gentamicin, tobramycin, sisomicin, benzamycin (dibekacin), kanamycin B (bekanamycin, micronomicin, etc.), tetracycline antibiotics (oxytetracycline, etc.), macrolide antibiotics (erythromycin etc.), chloramphenicol (chloramphenicol)-based antibacterial drugs (chloramphenicol, etc.), polypeptide (polypeptide)-based antibacterial drugs (colistin (colistin) ), acyclovir, adenine arabinoside, ganciclovir, foscarnet, valaciclovir, trifluorothymidine, Dofovir (cidofovir, carbocyclic oxetanocin G, etc.), antifungal drugs (streptomycin (pimaricin), fluconazole (fluconazole), itraconazole (itraconazole), miconazole ( miconazole), flucytosine (flucytosine), amphotericin (amphotericin) B, etc.), etc.

Sugars: Examples include lactulose, raffinose, pullulan, glucose, maltose, trehalose, sucrose, cyclodextrin, and xylose alcohol, mannitol, sorbitol, etc.

Polysaccharides or derivatives thereof: For example, gum arabic, caraya gum, xanthan gum, carob gum, guar gum, guaiac, quince seed, dammar gum ( dammar gum), tragacanth, benzoin gum, locust bean gum, casein, agar, alginic acid, dextrin, dextran, carrageenan, gelatin, collagen, fruit Glue, starch, polygalacturonic acid (alginic acid), chitin and its derivatives, chitosan and its derivatives, elastin, hyaluronic acid, sulfuric acid Chondroitin or its salt (sodium alginate, chondroitin sodium sulfate, etc.), etc.

Local anesthetic ingredients: examples include lidocaine, oxybuprocaine, dibucaine, procaine, ethylaminobenzoate, and meprocaine (meprylcaine), mepivacaine, bupivacaine, cocaine, and their salts (lidocaine hydrochloride, oxybucaine hydrochloride, etc.), and the like.

Steroid components: For example, hydrocortisone (hydrocortisone), Prednisolone, cortisol, methylprednisolone, triamcinolone, paramethasone, betamethasone, and the some salt etc.

Glaucoma treatment ingredients: for example, distigmine bromide, timolol maleate, carteolol hydrochloride, betaxolol hydrochloride, laxyl latanoprost, isopropyl unoprostone, dipivefrin hydrochloride, apraclonidine hydrochloride, pilocarpine hydrochloride, carbamide Choline (carbachol), dorzolamide hydrochloride (dorzolamide hydrochloride), acetazolamide (acetazolamide), methazolamide (methazolamide), and their salts.

Cataract treatment ingredients: for example, pirenoxine, glutathione, salivary gland hormone, tiopronin, dihydroazapentacene disulfonate and the Some salts (such as 5,12-dihydroazapentacene disulfonate sodium (Sodium5,12-dihydro azapentacene disulfonate), etc.), etc.

Mydriatic components: for example, cyclopentolate hydrochloride, tropicamide, etc. can be mentioned.

In the case of compounding drugs, the compounding amount can be selected from the effective adaptable amount of each drug, but in terms of eye irritation and composition stability, it is preferably 0.001w in ophthalmic compositions /v%~5w/v% range.

Examples of the buffer include citric acid, sodium citrate, boric acid, borax, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, acetic acid, sodium acetate, glacial acetic acid, trometamol, Sodium carbonate, sodium bicarbonate, etc. In the case of preparing a buffer, the amount of the buffer is preferably in the range of 0.003w/v% to 4w/v% in the ophthalmic composition.

Examples of stabilizers include: ethylenediamineacetic acid derivatives or salts thereof (such as edetic acid (ethylenediaminetetraacetic acid, etc.), edetate sodium (ethylenediaminetetraacetic acid, etc.), α-cyclodextrose Ethyl alcohol, β-cyclodextrin, γ-cyclodextrin, etc. In the case of compounding a stabilizer, its compounding amount is preferably in the range of 0.003w/v% to 2w/v% in the ophthalmic composition.

Examples of the viscous agent include cellulose-based polymer compounds such as methyl cellulose, hypromellose, and hydroxyethyl cellulose; polyvinyl pyrrolidone (povidone), polyvinyl alcohol, and the like; It is a polymer compound; liquid paraffin, carboxy vinyl polymer, polyethylene glycol, etc. In the case of compounding a viscous agent, its compounding amount is preferably in the range of 0.003w/v% to 3w/v% in the ophthalmic composition.

Examples of tonicity agents include potassium chloride, sodium chloride, calcium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium carbonate, magnesium sulfate, disodium hydrogenphosphate, sodium dihydrogenphosphate, sodium hydrogensulfite, etc. . In the case of compounding a tonicity agent, its compounding amount is preferably in the range of 0.001w/v% to 3w/v% in the ophthalmic composition.

As an antioxidant, hydroquinone, propyl gallate, sodium bisulfite, etc. are mentioned, for example. When an antioxidant is formulated, its formulation amount is preferably in the range of 0.001w/v% to 1w/v% in the ophthalmic composition.

Examples of preservatives include hydroxychloroaniline, benzolin chloride, lohexidine gluconate, sorbic acid, potassium sorbate, polidronium chloride, alkyldiaminoethylglycine hydrochloride acid, polyhexamethylene biguanide, etc. In the case of compounding a preservative, its compounding amount is preferably in the range of 0.001w/v% to 0.5w/v% in the ophthalmic composition.

As a pH adjuster, hydrochloric acid, sulfuric acid, phosphoric acid, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide etc. are mentioned, for example. The pH (20°C) of the ophthalmic composition of the present invention is 3.5-8.0, preferably 5.0-7.5, more preferably 6.0-7.3. When the pH is too low or too high, the irritation may become stronger. In addition, the measurement of pH was performed at 20 degreeC using the pH osmometer (HSMO-1, Donga DKK Co., Ltd.). As a pH adjuster, sodium hydroxide, potassium hydroxide, hydrochloric acid, etc. are preferable.

As a polyhydric alcohol, glycerin, propylene glycol, butylene glycol, polyethylene glycol, etc. are mentioned, for example.

[Production method]

The ophthalmic composition of the present invention can be produced, for example, by a known production method with the balance being water. For example, it can be obtained by adjusting the pH after dissolving the above-mentioned components in a mixed solvent such as sterilized purified water, ion-exchanged water, etc. Press and so on.

[Ophthalmic Products]

The ophthalmic product of the present invention is formed by storing the ophthalmic composition in a container, and enclosing and sealing the container together with an iron-based oxygen absorber with an encapsulating body, the container containing the ophthalmic composition In the ophthalmic product, the capacity of the body is 1mL~25mL, the oxygen transmission rate of the body is 10cc/( ^m2.24hr.atm ) or more, formed in the encapsulation The volume of the space between the container and the container is 200 V/V% or less relative to the volume of the container.

The container includes a main body and a lid for containing the ophthalmic composition. More specifically, the main body is provided with an eye drop opening, and has a cover body such as a screw-type or a one-touch type that seals the main body. Furthermore, an inner plug having an eye drop opening can also be provided in the body, and the eye drop opening can also be provided in the cover body, or the cover body can be directly provided on the container so as to be airtight. Preferably, an inner plug having an eye drop opening is provided in the main body. In the present invention, the term "container" refers to a state in which a lid is attached to a main body.

<body>

In order to volatilize the cooling agent in the ophthalmic composition into the encapsulated body, the oxygen transmission rate of the body containing the ophthalmic composition is 10 cc/(m ² .24 hr.atm) or more. The upper limit is not particularly limited, but may be 200 cc/(m ² .24 hr.atm) or less. Specific examples of the body having such an oxygen permeability include polyethylene, polyethylene terephthalate, polypropylene, polybutene, polycarbonate, polyacrylate, vinyl chloride, and the like. ontology. More specifically, a multi-dose eye drop container made of polyethylene terephthalate is more preferable because of its high stability. The oxygen transmission rate can be measured by a method according to Japanese Industrial Standards (JIS)-K7126-2 plastic film and plastic sheet-gas transmission rate test method B (Appendix B).

The volume of the main body (the volume when the main body is filled with the ophthalmic composition) is 1mL-25mL, preferably 5mL-20mL. Furthermore, the amount of the ophthalmic composition to be contained can be appropriately selected according to the product and its usage method, for example, in the case of multi-dose eye drops, it is 1 mL to 25 mL, preferably 1 mL to 20 mL, more preferably 5 mL to 20 mL . When the amount of the ophthalmic composition is too small, the volatilization amount of the cooling agent in the eye drop container may be insufficient, and the odor masking effect may be insufficient.

<Cover body, inner plug>

As the inner plug and the cap, caps made of materials used in conventional ophthalmic product containers can be used. The material of the inner plug is preferably polyethylene or polypropylene with a melt flow rate of 2.0 or less, preferably 1.2 to 1.8. As a material of the cover body, polyethylene and polypropylene are preferable.

The oxygen permeability of the container is preferably at least 0.01%, more preferably at least 0.1%, still more preferably at least 0.2%. The upper limit is not particularly limited, and may be, for example, 5% or less. In addition, the measuring method of oxygen permeability is the method described in the Example mentioned later. When the oxygen permeability is high, the cooling agent is easy to volatilize, and the odor masking effect can be further obtained.

The filling rate of the ophthalmic composition relative to the volume of the container (in a container equipped with a lid and an inner plug, the volume ratio of the empty wall of the main body to the full volume of the container) is preferably 50% or more, more preferably 70% or more, and more preferably 80% or more. If the containment rate is too low, the cooling agent will be filled in the cavity, and the masking effect of the odor in the enclosed body may be insufficient.

[oxygen absorber]

The oxygen absorbing agent of the present invention is an iron-based oxygen absorbing agent. Specifically, Ageless (FX, SA, Z-PT, GL, G) manufactured by Mitsubishi Gas Chemical Co., Ltd., Vitalon manufactured by Tokiwa Industry Co., Ltd., etc. Use a specification that sufficiently absorbs oxygen in the capsule. In general, oxygen absorbers are widely used in pharmaceuticals. In the food industry, it can be used at low cost. Furthermore, as the oxygen absorbing agent, one capable of absorbing all the oxygen present in the pillow is used. If it is below the above-mentioned capacity, oxygen cannot be sufficiently absorbed, and easily oxidized oxides will be oxidatively decomposed. If it is above the above-mentioned capacity, the pillow may shrink and the container may be dented.

[Encapsulation]

The ophthalmic composition is surrounded and sealed together with the oxygen absorbent. Examples of materials for the package include polyethylene, polyethylene terephthalate, polypropylene, polybutylene, polycarbonate, polyester, nylon, cellophane, polyvinyl chloride film, aluminum foil, or deposited Aluminum polyvinyl alcohol-based film, polyamide-based film, aluminum oxide-deposited polyethylene terephthalate, silicon oxide-deposited polyethylene terephthalate, polyethylene terephthalate coated with polydene Vinyl chloride films, laminated films, etc., composites of these, multilayer films, etc. Among them, a polyethylene terephthalate/polyethylene multilayer film and a polyethylene terephthalate/polyethylene multilayer film on which aluminum oxide is vapor-deposited are preferred. The oxygen transmission rate is preferably below 10cc/(m ² .24hr.atm) (ie 0~10cc/(m ² .24hr.atm)). Furthermore, the oxygen transmission rate of the encapsulation is ideally lower than that of the body, more preferably less than 10cc/(m ² .24hr.atm), further preferably 0~3cc/(m ² .24hr.atm). atm), 0~1cc/(m ² .24hr.atm), 0.01cc/(m ² .24hr.atm)~0.3cc/(m ² .24hr.atm), especially 0.01cc/(m ² .atm) 24hr.atm) ~ 0.1cc/(m ² .24hr.atm), the best is 0.01cc/(m ² .24hr.atm) ~ 0.02cc/(m ² .24hr.atm).

The volume of the space (internal space) formed between the envelope and the container (with the lid attached to the body) is 200 V/V% or less relative to the volume of the container, preferably Below 150V/V%, more preferably below 120V/V%. If it exceeds 200 V/V%, the masking effect of the odor in an encapsulated body cannot fully be acquired. The lower limit is not particularly limited, and may be 20 V/V% or more.

[masking method]

The present invention provides a masking method for masking the odor when an encapsulated body is unsealed in an ophthalmic product. The ophthalmic product contains an ophthalmic composition in a container, and the container and iron The oxygen absorbing agent of the system is surrounded and sealed together. The container includes a body and a cover for containing the ophthalmic composition. The ophthalmic composition includes: (A) easily oxidizing agent, (B) cooling agent, (C) nonionic surfactant, and (D) one selected from dibutyl hydroxytoluene, dibutyl hydroxyanisole, propyl peroxybenzoate, butyl peroxybenzoate and chlorobutanol The above ingredients, the masking method is in the ophthalmic product, the volume of the body is set to 1mL~25mL, and the oxygen transmission rate of the body is set to 10cc/(m ² .24hr.atm) or more, The volume of the space formed between the envelope and the container is 200 V/V% or less relative to the volume of the container. Preferred components, ranges, etc. are the same as above.

[Example]

Hereinafter, although an Example and a comparative example are shown and this invention is concretely demonstrated, this invention is not limited to a following example. In addition, in the following examples, unless otherwise specified, "%" of a composition shows w/v% (g/100mL), and a ratio shows a mass ratio.

[Example, comparative example]

The ophthalmic composition of the composition shown in the following table is produced according to the usual method, and stored in the following container, and then mixed with an oxygen absorber (Ageless (Model: Z-PT15), Mitsubishi Gas Chemical Co., Ltd.) were packaged together, film-packed and sealed using the following encapsulated body, and an ophthalmic product was obtained. The ophthalmic products at 40 ℃. It can be stored for one month under the environment of 75%RH. After storage, the film package was opened, and the sensory evaluation of the following odor was implemented.

In addition to Example 2, Comparative Example 3, Comparative Example 4 and Comparative Example 5, the following containers were used. Encapsulation.

<container>

． ontology

Material: polyethylene terephthalate; oxygen transmission rate 10cc/(m ² .24hr.atm)

The capacity of the body: 17mL

． Cover

Spiral

． Nese

<Encapsulation>

Material: Polyethylene terephthalate/polyethylene multilayer film with aluminum oxide deposited (oxygen transmission rate 0.2cc/(m ² .24hr.atm))

Size: W9.0×L6.5(cm)

Use the container. Each condition in the case of an encapsulated body is as follows.

． Amount of ophthalmic composition: 15mL

． Container oxygen permeability: 0.7%

． Filling rate of the ophthalmic composition relative to the volume of the container: 88%

． Container volume: 22mL

． Space formed between the capsule and the container (inner space): 23 mL

． Internal space ratio relative to container volume: 105%

In Example 2 and Comparative Example 4, the size of the encapsulated body was changed so as to become the internal space ratio with respect to the container volume in the table, and in Comparative Example 3, the composition amount (mL)/body capacity ( mL) so as to be the space ratio in the table, in Comparative Example 5, a non-oxygen permeable material was used as the main body.

[Measuring method of container oxygen permeability]

(1) Put the empty container into the capsule at room temperature (20°C~30°C). Install the inner plug on the container. cover body. Regarding the oxygen permeability of the encapsulated body, an encapsulated body with low oxygen permeability having an oxygen permeability of 0.2 cc/(m ² .24 hr.atm) or less is used. The size of the capsule was 150 mm×65 mm (inner dimension).

(2) The space between the container and the envelope is filled with nitrogen and sealed. Nitrogen at this time The conversion rate is set to 90% by volume or more (the oxygen concentration is 2% by volume or less).

(3) Heat-sealing was performed so that the size of the envelope would be 85 mm×65 mm (inner dimension), and the envelope was divided into two spaces. The oxygen concentration in the space of the capsule on the side without the container was measured and set as an initial value. For the oxygen concentration, a residual oxygen concentration meter (Iijima Electronics Co., Ltd.) was used.

(4) At 40°C. Stored under the condition of 75%RH for 3 days, after taking it out and placing it at room temperature, the oxygen concentration in the capsule was measured.

The value calculated by the following calculation formula was defined as oxygen permeability.

Oxygen permeability calculation formula: Oxygen permeability (%) = Oxygen concentration in the envelope after storage (%) - Initial oxygen concentration in the envelope (%)

[evaluation of the smell]

About odor, sensory evaluation was performed by the expert sensory tester in the following 4 stages (n=6).

0: Odor is remarkably felt

1: Odor is felt

2: Slightly smelly

3: Smell is hardly felt

4: Abnormal smell is not sensed at all

5: There is no peculiar smell and the smell of cooling agent is felt

The obtained results (average values) are described together with the following evaluation criteria based on them. ●, ○, and ◎ were set as pass.

<Evaluation criteria>

×: less than 1.5

●: more than 1.5, less than 2.0

○: 2.0 or more, less than 3.0

◎: 3.0 or above

[Table 4]

[Table 6]

[Table 8]

Furthermore, when the material of the envelope was changed to polyethylene (oxygen permeability: 3 cc/(m ² .24 hr.atm)), the same result as above was obtained.

The raw materials used in the above examples are shown below. In addition, unless otherwise indicated, the quantity of each component in a table|surface is a purity conversion quantity.

Retinyl palmitate: (trade name: Retinyl palmitate, manufactured by DSM Nutrition Japan (stock), 1.74 million I.U/g)

l-menthol: (a brand name: l-menthol (menthol), product made in Suzuki Mint Co., Ltd.)

dl-camphor: (trade name: Japanese Pharmacopoeia dl-camphor, manufactured by Nippon Seika Co., Ltd.)

d-Camphor: (trade name: Japanese Pharmacopoeia d-Camphor, manufactured by Nippon Seika Co., Ltd. make)

d-borneol: (trade name: extra-boiled borneol (d-borneol), manufactured by Masami Yanagisawa Co., Ltd.)

Eucalyptus Oil: (trade name: Japanese Pharmacopoeia Eucalyptus Oil, Ogawa Fragrance (stock))

Geraniol: (trade name: Geraniol EX MIX, manufactured by Takasago Fragrance Industry Co., Ltd.)

Polyoxyethylene hydrogenated castor oil 60: (trade name: HCO-60 (for medical use), manufactured by Japan Surfactant Industry Co., Ltd.)

Polyoxyethylene hydrogenated castor oil 40: (trade name: HCO-40 (for medical use), manufactured by Japan Surfactant Industry Co., Ltd.)

Polyoxyethylene (20) sorbitan oleate (polysorbate 80): (trade name: Rheodol TW-O120V, manufactured by Kao Co., Ltd.)

Polyoxyethylene polyoxypropylene diol (polyoxyethylene (196) polyoxypropylene (67) diol): (trade name: Kolliphor P407, manufactured by BASF Japan Co., Ltd.)

Polyethylene glycol monostearate (polyethylene glycol stearate 40): (trade name: NIKKOL MYS-40MV, manufactured by Japan Surfactant Industry Co., Ltd.)

Dibutylhydroxytoluene: (trade name: dibutylhydroxytoluene, manufactured by Wako Pure Chemical Industries, Ltd.)

Propyl peroxybenzoate: (trade name: Mekkinsu-P, manufactured by Ueno Pharmaceutical Co., Ltd.)

Butyl peroxybenzoate: (trade name: Mekkinsu-B, manufactured by Ueno Pharmaceutical Co., Ltd.)

Chlorobutanol: (trade name: Chlorobutanol, JSC Olainfarm)

Claims (6)

An ophthalmic product, which is formed by storing an ophthalmic composition in a container, and enclosing and sealing the container together with an iron-based oxygen absorber with an encapsulating body, the container containing the ophthalmic composition The body and cover of the ophthalmic composition include: (A) easily oxidized, (B) cooling agents, (C) nonionic surfactants, and (D) selected from dibutyl hydroxytoluene, One or more of dibutyl hydroxyanisole, propyl peroxybenzoate, butyl peroxybenzoate and chlorobutanol, in the ophthalmic product, the capacity of the body is 1mL~25mL, so The oxygen permeability of the body is 10 cc/(m ² .24 hr.atm) or more, and the volume of the space formed between the envelope and the container is 200 V/V% or less relative to the volume of the container . The ophthalmic product as described in claim 1, wherein the component (A) is vitamin A. The ophthalmic product as described in item 1 or item 2 of the scope of the patent application, wherein the component (B) is selected from l-menthol, dl-camphor, d-camphor, d-borneol, geraniol and eucalyptus oil more than one of . The ophthalmic product as described in item 1 or item 2 of the patent application, wherein the compounding amount of component (B) in the ophthalmic composition is 0.0001w/v% or more. The ophthalmic product as described in item 1 or item 2 of the scope of the patent application, wherein component (C) is selected from polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene (20) sorbose One or more of alkyd oleate and polyoxyethylene polyoxypropylene glycol. A masking method for masking the odor when an encapsulated body is unsealed in an ophthalmic product. The ophthalmic product is to accommodate an ophthalmic composition in a container, and utilize the absorption of the container and the iron system by the encapsulated body. The oxygen agent is surrounded and sealed together. The container includes a body and a cover for containing the ophthalmic composition. The ophthalmic composition includes: (A) easily oxidized, (B) cooling agent, (C) Nonionic surfactant, and (D) one or more components selected from dibutyl hydroxytoluene, dibutyl hydroxyanisole, propyl peroxybenzoate, butyl peroxybenzoate, and chlorobutanol , the masking method is in the ophthalmic product, the capacity of the body is set to 1mL~25mL, the oxygen transmission rate of the body is set to 10cc/(m ² .24hr.atm) or more, formed in the The volume of the space between the envelope and the container is 200 V/V% or less relative to the volume of the container.